Event Reports Research Articles

Dry needling perceptions and experiences: A survey of Australian physiotherapists

BackgroundThere is a lack of information on the use of dry needling in Australian physiotherapy practice. ObjectivesOur primary aim was to enhance the understanding of why Australian physiotherapists use dry needling in clinical practice. The secondary aim was to explore Australian physiotherapists experiences with adverse events caused by dry needling. DesignCross-sectional online survey. MethodWe developed a survey and disseminated it through email to physiotherapists from all states and territories in Australia. Participant demographics and responses were reported as frequencies and percentages. Results/findingsWe invited 1006 Australian physiotherapists, of which 232 (23%) viewed the online survey and 203 (20%) consented to participate, of which nearly all completed the survey (n = 198, 98%). Most respondents worked in private practice (n = 164, 83%), with 127 (64%) reporting using dry needling as an intervention within the previous 12 months. Physiotherapists typically used dry needling to decrease pain intensity (n = 105, 85%) and reduce muscle tension (n = 100, 81%). Reports of minor adverse events were common and included discomfort during the treatment (n = 77, 62%) and bruising (n = 69, 56%). Some respondents reported experiencing major adverse events including prolonged aggravation of symptoms (n = 10, 8%) and syncope (n = 16, 13%). ConclusionsWe found that many Australian physiotherapists in private practice use dry needling, usually to decrease pain intensity and muscle tension. Minor adverse events were experienced by more than half the respondents and between 8 and 13% of the Australian physiotherapists surveyed reported experiencing a major adverse event due to dry needling.

Optimizing Signal Management in a Vaccine Adverse Event Reporting System: A Proof-of-Concept with COVID-19 Vaccines Using Signs, Symptoms, and Natural Language Processing.

The Vaccine Adverse Event Reporting System (VAERS) has already been challenged by an extreme increase in the number of individual case safety reports (ICSRs) after the market introduction of coronavirus disease 2019 (COVID-19) vaccines. Evidence from scientific literature suggests that when there is an extreme increase in the number of ICSRs recorded in spontaneous reporting databases (such as the VAERS), an accompanying increase in the number of disproportionality signals (sometimes referred to as 'statistical alerts') generated is expected. The objective of this study was to develop a natural language processing (NLP)-based approach to optimize signal management by excluding disproportionality signals related to listed adverse events following immunization (AEFIs). COVID-19 vaccines were used as a proof-of-concept. The VAERS was used as a data source, and the Finding Associated Concepts with Text Analysis (FACTA+) was used to extract signs and symptoms of listed AEFIs from MEDLINE for COVID-19 vaccines. Disproportionality analyses were conducted according to guidelines and recommendations provided by the US Centers for Disease Control and Prevention. By using signs and symptoms of listed AEFIs, we computed the proportion of disproportionality signals dismissed for COVID-19 vaccines using this approach. Nine NLP techniques, including Generative Pre-Trained Transformer 3.5 (GPT-3.5), were used to automatically retrieve Medical Dictionary for Regulatory Activities Preferred Terms (MedDRA PTs) from signs and symptoms extracted from FACTA+. Overall, 17% of disproportionality signals for COVID-19 vaccines were dismissed as they reported signs and symptoms of listed AEFIs. Eight of nine NLP techniques used to automatically retrieve MedDRA PTs from signs and symptoms extracted from FACTA+ showed suboptimal performance. GPT-3.5 achieved an accuracy of 78% in correctly assigning MedDRA PTs. Our approach reduced the need for manual exclusion of disproportionality signals related to listed AEFIs and may lead to better optimization of time and resources in signal management.

Literature Review of Safety Event Reporting in Observational Studies: Challenges Extrapolating across Comparable Products

Nirmatrelvir/ritonavir (PAXLOVIDTM, Pfizer) is an anti-infective inhibiting CYP3A4 indicated for the treatment of COVID-19 in adults at increased risk of severe COVID-19. As a newly approved product, PAXLOVID has limited safety information regarding rare events and serious adverse events (SAEs). This review describes the characterization of the real-world safety profile of products with similar pharmacological properties to PAXLOVID and aims to understand the impact of any drug interaction on the concomitantly prescribed products. A literature search of articles in PubMed published between 2018 and 2023 was conducted to assess the real-world frequency of safety outcomes of interest, specifically those meeting the criteria of serious adverse reaction. The review was restricted to observational, noninterventional studies and included CYP3A4 inhibitors prescribed for short-term treatment of infections in the outpatient setting. Twenty-one articles were included in the review. Most focused on a small, predefined list of safety outcomes and did not provide insight into the broader range of safety outcomes that might occur for the evaluated products with similar pharmacological properties to PAXLOVID or the impact of any interaction on the concomitant product. The findings highlight the challenges in obtaining proxy safety outcomes characteristics via a review of products with comparable pharmacological properties and underscore the need to have large, rapidly accessible data sources that can contribute to the safety profile of newly authorized products in the real world.

Incidence of anaphylaxis to YF-VAX® yellow fever vaccination: a retrospective evaluation of vaccine adverse event reports 1999-2018.

The incidence of anaphylaxis after receipt of yellow fever (YF) vaccine is highly variable based upon previously published reports. Anaphylaxis after receiving the YF vaccine has been reported to range from 0 up to 22 per 1 000 000 doses. Our clinical experience suggested increased incidence, which prompted our investigation. We sought to evaluate the current incidence rate of anaphylaxis after receipt of the 17D-204 strain YF-VAX® brand reported in the US. We performed a retrospective review of the Vaccine Adverse Event Reporting System (VAERS) reports of anaphylaxis after receiving the YF-VAX vaccine occurring between 1 October 1999 and 30 September 2018. We utilized the Brighton Collaboration Case Definition and inclusion determination was made by a board-certified allergist. We also obtained the total number of YF-VAX doses distributed across the US during this same time-period and then calculated an updated incidence rate of YF-VAX vaccine-associated anaphylaxis. We identified 132 potential cases of possible or probable anaphylaxis. Of these, 111 met inclusion criteria: level 1 (n = 51), level 2 (n = 59) and level 3 (n = 1). The manufacturer reported a total distribution of 7 624 160 doses of YF-VAX from 1 October 1999 to 30 September 2018. The calculated incidence rate of YF-VAX vaccine-associated anaphylaxis is estimated at 14.6 events per 1 000 000 doses. We conclude the estimated rate of anaphylaxis per VAERS reports is 14.6 events per 1 000 000 doses after YF-VAX vaccination. This is consistent with some previous reports and substantially higher than rates of anaphylaxis after other vaccines.

Adverse events related to triplanar 1st tarsometatarsal joint arthrodesis: 5-year analysis of the united states food and drug administration manufacturer and user facility device experience database

BackgroundThe Lapiplasty® 3D Bunion Correction™ system represents an instrumented, jig-guided system to facilitate performing triplanar 1st tarsometatarsal joint arthrodesis. Literature available for this system is positive, although the vast majority is from inventor/consultant surgeons. The purpose of this manuscript is to review adverse event submissions recorded in the Manufacturer and User Facility Device Experience database specific to this system. MethodsThe Manufacturer and User Facility Device Experience database was retrospectively reviewed from inception to 30 June 2023 for adverse events submitted for the Lapiplasty® 3D Bunion Correction™ system. Submissions that involved a medical device product other than this system, duplicate entries, and submissions with data extracted from already published literature were excluded. ResultsA total of 180 unique reports that met inclusion criteria during the 5-year period available were reviewed. The mean time between event occurrence and submission was 46.7-days. The most common entity submitting to the database were the manufacturer company representative or distributor in 66.4%. The most frequently encountered patient problems were pain in 41.9%, non-union in 18.2%, and hardware-related irritation in 11.7%. Reports that detailed a revision surgery described partial/complete hardware removal in 62.7% and revision with additional hardware implantation in 23.3%. ConclusionWhile no direct conclusions regarding the Lapiplasty® 3D Bunion Correction™ system can be drawn from the data as it consists of only adverse event reports, this study demonstrates the need for more non-inventor/consultant literature to further investigate adverse events related this particular system.

Antibiotics and antibiotic-associated diarrhea: a real-world disproportionality study of the FDA adverse event reporting system from 2004 to 2022

Background Our study aimed to assess the risk signals of antibiotic-associated diarrhea (AAD) caused by various antibiotics using real-world data and provide references for safe clinical applications.Methods We analyzed data extracted from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the third quarter of 2022. We computed the reporting odds ratio (ROR) for each antibiotic or antibiotic class to compare the signal difference. Furthermore, we also examined the differences in the onset times and outcomes of AAD caused by various antibiotics.ResultsA total of 5,397 reports met the inclusion requirements. Almost all antibiotics, except tobramycin and minocycline (ROR 0.98; 95%CI: 0.64–1.51 and 0.42; 95%CI: 0.16–1.11, respectively), showed a significant correlation with AAD. The analysis of the correlation between different classes of antibiotics and AAD revealed that lincomycins (ROR 29.19; 95%CI: 27.06–31.50), third-generation cephalosporins (ROR 15.96; 95%CI: 14.58–17.47), and first/second generation cephalosporins (ROR 15.29; 95%CI: 13.74–17.01) ranked the top three. The ROR values for antibiotics from the same class of antibiotics also varied greatly, with the ROR values for third-generation cephalosporins ranging from 9.97 to 58.59. There were also differences in ROR values between β-lactamase inhibitors and their corresponding β-lactamase drugs, such as amoxicillin-clavulanate (ROR = 13.31; 95%CI: 12.09–14.65) and amoxicillin (ROR = 6.50; 95%CI: 5.69–7.44). 91.35% of antibiotics have an onset time of less than four weeks.ConclusionsThere is a significant correlation between almost all antibiotics and AAD, particularly lincomycins and β-lactam antibiotics, as well as a different correlation within the same class. These findings offer valuable evidence for selecting antibiotics appropriately.

Effect of acid suppressant medications on the laxative action of magnesium preparations in patients with opioid-induced constipation: A pharmacovigilance analysis of the FDA Adverse Event Reporting System.

Objective: Magnesium oxide is widely used for treating opioid-induced constipation, a serious analgesic-associated problem. Opioid analgesic users are often prescribed non-steroidal anti-inflammatory drugs, which are sometimes combined with acid suppressants to prevent gastrointestinal adverse events. Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect. This study was aimed at evaluating the effect of magnesium preparations combined with acid suppressants on the incidence of opioid-induced constipation by using the Food and Drug Administration Adverse Event Reporting System. Methods: Adverse events were defined per the Medical Dictionary for Regulatory Activities; the term 'constipation (preferred term code: 10010774)' was used for analysis. After adjusting for patient background factors using propensity score matching, acid suppressants' effect on constipation incidence was evaluated in opioid users prescribed magnesium preparations alone as laxatives by using a test for independence. Key Findings: The Food and Drug Administration Adverse Event Reporting System contains 14,475,614 reports for January 2004 to December 2021. Significantly increased constipation incidence was related to magnesium preparations combined with acid suppressants, especially proton pump inhibitors (P < 0.0001, McNemar's test). Conclusion: Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect; healthcare professionals should pay attention to this issue.

New exploration of signal detection of Regional Risks from the perspective of data mining: a pharmacovigilance analysis based on spontaneous reporting data in Zhenjiang, China

ABSTRACT Background This study aimed to adopt the conventional signal detection methods to explore a new way of risk identification and to mine important drug risks from the perspective of big data based on Zhenjiang Adverse Event Reporting System (ZAERS). Research design and methods Data were extracted from ZAERS database between 2012 and 2022. The risks of all the reported drug event combinations were identified at the preferred term level and the standardized MedDRA query level using disproportionality analysis. Then, we conducted signal assessment according to the descriptions of drug labels. Results In total 41,473 ADE were reported and there were 12 risky signals. Signal assessment indicates the suspected causal associations in clindamycin-taste and smell disorders, valsartan-hepatic enzyme increased and valsartan-edema peripheral; the specific manifestations of allergic reactions triggered by clindamycin, cefotaxime, cefazodime, ShexiangZhuanggu plaster, ShexiangZhuifeng plaster, and Yanhuning need to be refined in drug labels. In addition, the drug labels of NiuHuangShangQing tablet/capsule, Fuyanxiao capsule, and BiYanLing tablet should be improved. Conclusions In this study, we attempted a new way to find potential drug risks using small spontaneous reporting data. Our findings also suggested the need for more precise identification of allergic risks and the improvement of traditional Chinese medicine labels.

Just Culture: How Do We Address Risky and Unprofessional Behaviors that Lead to Errors?

Unprofessional behavior in the procedural arena is associated with worse patient outcomes. This is thought to be due to breakdowns in communication structures and team dynamics. Behavioral issues are often uncovered during the investigation of serious event reports. Understanding differences in behavior deviations enables leadership to best address each type with an appropriate response. This allows institutions to address reckless behavior and unprofessionalism, while concomitantly creating a culture that fosters trust to promote self-reporting and sharing of information. These are characteristics of high-reliability organizations that produce sustained excellence in patient outcomes.

Ocular Surface Adverse Events are not Associated with Dupilumab use in Nasal Polyp Treatment.

Ocular surface reactions (OSR) have been associated with dupilumab for atopic dermatitis (AD) treatment. However, the association of dupilumab-associated OSR (DA-OSR) for nasal polyps (CRSwNP) treatment has not been studied. We evaluated DA-OSR for CRSwNP treatment using the FDA Adverse Event Reporting System (FAERS). FAERS was queried for any general ocular reactions (DA-GOR) from 2019Q1 to 2022Q4. DA-OSR were subcategorized from DA-GOR and compared between treatment groups (CRSwNP, asthma, AD). Logistic regression was used to predict DA-OSR. Disproportionality analysis (DPA) of DA-OSR was performed using OpenVigil. There were 60,198 total observations, of which 5344 were treated for CRSwNP. The prevalence of DA-GOR and DA-OSR was greatest for AD (15.3%, 7.8%), followed by CRSwNP (12.2%, 6.7%) and asthma (9.2%, 3.5%). The most commonly reported OSRs were dry eyes (35.9%), conjunctivitis (15.7%), and increased lacrimation (11.0%). The reported odds ratio (ROR) of CRSwNP-treated DA-OSR was 0.84 (0.73-0.97; p = 0.015), compared to 1.29 (1.20-1.40; p < 0.001) for AD and 0.66 (0.59-0.73; p < 0.001) for asthma. For CRSwNP treatment, the DA-OSR ROR was 0.97 (0.90-1.03; p = 0.3) for men and 0.78 (0.73-0.83, p < 0.001) for older adults (age > 50). ROR in the DPA for DA-OSR was 12.5 (12.2-12.8; p < 0.001) for any indication and 0.58 (0.53-0.64; p < 0.001) for CRSwNP treatment only. While there are limitations to FAERS, this study confirms the association between dupilumab and OSR for AD treatment, and does not support an association between dupilumab and OSR for CRSwNP treatment. Younger adults experience more DA-OSR in CRSwNP treatment without a specific predilection for sex. IV Laryngoscope, 134:2602-2608, 2024.

Concomitant Use of Multiple Nephrotoxins including Renal Hypoperfusion Medications Causes Vancomycin-Associated Nephrotoxicity: Combined Retrospective Analyses of Two Real-World Databases.

There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51-1.85]; VCM + ≥2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37-1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42-2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN.

Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.

Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.

Novel perspective on cardiovascular adverse event profiles due to treatment with sodium-glucose transport protein 2 (SGLT2) inhibitors in the Japanese Adverse Drug Event Report (JADER) database

Novel perspective on cardiovascular adverse event profiles due to treatment with sodium-glucose transport protein 2 (SGLT2) inhibitors in the Japanese Adverse Drug Event Report (JADER) database

Strong opioids-induced cardiac, neurologic, and respiratory disorders: a real-world study from 2004 to 2023 based on FAERS.

Opioids are mainly used as adjuncts to the induction and maintenance of general anesthesia, postoperative analgesia, and treating moderate to severe cancer pain and chronic pain. However, the hazards of these drugs to various organ organs still need to be further explored. This study used the US FDA Adverse Event Reporting System (FAERS) database to determine whether commonly receiving opioids was higher than the baseline risk for all other medications. FAERS was asked about adverse events (AEs) for the opioids "morphine," "fentanyl," "oxycodone," "hydromorphone," "sufentanil," and "remifentanil" from the first quarter of 2004 (2004Q1) through the second quarter of 2023 (2023Q2). Disproportionality signaling analysis was performed by calculating reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). AEs with system organ classes (SOCs) of "cardiac disease," "neurologic disease," and "respiratory, thoracic, and mediastinal disease" were then screened. The statistical analysis included 12,819,518 reports in the FAERS database from 2004Q1 to 2023Q2, of which 236,619 AEs were reported as "primary suspect" for the six drugs mentioned above, which were selected as "cardiac disorders," "nervous system disorders," and "respiratory, thoracic and mediastinal disorders." Some AEs identified in this study are consistent with the drug labeling, such as bradycardia, respiratory depression, and somnolence. In addition, some unexpected and significant acute adverse drug reactions (ADRs), such as toxic leukoencephalopathy and coma, may occur. This study identified potential new and unexpected ADRs for opioids, providing valuable evidence for safety studies of opioids.

Proton Pump Inhibitors Ameliorate Oxaliplatin-induced Peripheral Neuropathy: Retrospective Analysis of Two Real-world Clinical Databases.

Chemotherapy-induced peripheral neuropathy (CIPN) due to oxaliplatin (L-OHP) is a major clinical problem. Effective and safe preventive strategies for CIPN are urgently needed. Although proton pump inhibitors (PPIs) have various off-target effects, their clinical impact on L-OHP-induced CIPN remains unclear. In the present study, we investigated the effects of PPIs on L-OHP-induced CIPN in patients using two real-world clinical databases. We retrospectively analyzed the electronic medical records of Osaka University Hospital to examine the effect of PPIs on CIPN development in 217 patients who received XELOX (L-OHP plus capecitabine) therapy for colorectal cancer. In addition, the Japanese Adverse Drug Event Report (JADER) database was used to validate the effects of PPIs on L-OHP-induced CIPN. The incidences of CIPN (grade ≥2) and discontinuation of L-OHP were significantly lower in patients with PPIs than in those without PPIs. Multivariate analysis showed that concomitant PPIs use was an independent factor that significantly contributed to the prevention of grade ≥2 CIPN (odds ratio=0.054, p<0.001). Kaplan-Meier analysis showed that the time to onset of grade ≥2 CIPN was significantly prolonged in patients with PPIs without affecting the therapeutic efficacy of L-OHP (p=0.004). Moreover, JADER database analyses revealed that the reporting odds ratio of any PPI for L-OHP-induced CIPN was 0.485. Concomitant PPI use ameliorated L-OHP-induced CIPN in patients with colorectal cancer.

Immunosuppressant Drug-Associated Non-Hodgkin Lymphoma: A Real-World Pharmacovigilance Database Analysis

Background: The association between immunosuppressant drugs and lymphoma has been reported frequently; however, the precise relationship remains uncertain. Non-Hodgkin lymphoma (NHL) is among the most common cancers associated with long-term immunosuppressant drug use. The FDA Adverse Event Reporting System (FAERS) is a publicly available tool that collects reports of adverse events from healthcare professionals, manufacturers and consumers. Methods: Nine immunosuppressant drugs belonging to different classes were shortlisted . The FAERS database was searched for all types of NHL as an adverse event reported between 2013 and 2022. Reporting odds ratio (ROR) was used to measure disproportionality in reporting of adverse events for these drugs. Results: When NHL was analyzed as a percentage of all cancers reported for a particular drug,azathioprine had the highest percentage (22.14%) followed by methotrexate (18.94%), mycophenolate (14.04%), infliximab/biosimilars (11.22%), cyclosporine (10.71%), etanercept (10.44%), tacrolimus (10.13%), adalimumab/biosimilars (8.80%) and sirolimus (8.51%). Drugs with highest ROR for NHL included azathioprine (2.09, 95% CI 1.94-2.24) followed by methotrexate (1.90, 95% CI 1.82-1.98) and azathioprine (1.17, 95% CI 1.10-1.25). Drugs with lowest ROR for NHL included adalimumab/biosimilars (0.62, 95% CI 0.59-0.65) followed by sirolimus (0.66, 95% CI 0.54-0.80) and tacrolimus (0.78, 95% CI 0.73-0.84). Conclusions: Although all immunosuppressive drugs have been associated with an increased risk of developing NHL, it is advisable to exercise caution with prescribing azathioprine, methotrexate and mycophenolate in patients with preexisting risk. While the use of adalimumab is an independent risk factor for the development of lymphoma, it had the lowest odds of NHL compared to other immunosuppressant drugs in the study. Prospective studies are needed to better understand the true incidence of NHL associated with immunosuppressant drugs.

Evidence and Mechanisms for Embolic Stroke in Contralateral Hemispheres From Carotid Artery Sources.

Disambiguation of embolus pathogenesis in embolic strokes is often a clinical challenge. One common source of embolic stroke is the carotid arteries, with emboli originating due to plaque buildup or perioperatively during revascularization procedures. Although it is commonly thought that thromboemboli from carotid sources travel to cerebral arteries ipsilaterally, there are existing reports of contralateral embolic events that complicate embolus source destination relationship for carotid sources. Here, we hypothesize that emboli from carotid sources can travel to contralateral hemispheres and that embolus interactions with collateral hemodynamics in the circle of Willis influence this process. We use a patient-specific computational embolus-hemodynamics interaction model developed in prior works to conduct an in silico experiment spanning 4 patient vascular models, 6 circle of Willis anastomosis variants, and 3 different thromboembolus sizes released from left and right carotid artery sites. This led to a total of 144 different experiments, estimating trajectories and distribution of approximately 1.728 million embolus samples. Across all cases considered, emboli from left and right carotid sources showed nonzero contralateral transport (P value <-0.05). Contralateral movement revealed a size dependence, with smaller emboli traveling more contralaterally. Detailed analysis of embolus dynamics revealed that collateral flow routes in the circle of Willis played a role in routing emboli, and transhemispheric movement occurred through the anterior and posterior communicating arteries in the circle of Willis. We generated quantitative data demonstrating the complex dynamics of finite size thromboembolus particles as they interact with pulsatile arterial hemodynamics and traverse the vascular network of the circle of Willis. This leads to a nonintuitive source-destination relationship for emboli originating from carotid artery sites, and emboli from carotid sources can potentially travel to cerebral arteries on contralateral hemispheres.

Sars-Cov-2 and Chronic Myeloid Leukemia: A Systematic Review

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing the coronavirus disease of 2019. Numerous mutations had developed in SARS-CoV-2 virus that resulted in strains (Alfa Beta Delta Omicron) with varying degrees of virulence disease severity. In coronavirus disease of 2019 (COVID-19) patients with chronic myeloid leukemia (CML), there is a controversy regarding the effect of tyrosine kinase inhibitors (TKI) on SARS-CoV-2 infection and patients' outcomes. Some studies showed that CML patients with COVID-19 had better outcomes; other reports showed no significant difference. Method Following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, PubMed, Scopus, and Google Scholar databases were searched for published articles through 20 April 2023 for qualified studies. The search included retrospective, prospective studies, reviews, case series, and case reports. The inclusion criteria were English literature with CML patients above 18 years who had SARS-CoV-2 infection. Articles in languages other than English and articles with non-sufficient information were excluded, and patients with bone marrow transplants were excluded. Search terms were (chronic myeloid leukemia) OR (chronic myelogenous leukemia) AND (SARS-CoV-2) OR (COVID-19). Two eligibility checks were done on the included studies. Title and abstract screening was completed first, and the full text of articles that met the requirements for inclusion was subsequently obtained. The search included all articles published up to 20 April 2023. The review is registered in PROSPERO (registration number is: CRD42022326674). Results We reviewed 36 articles of published literature up to April 2023 and collected data for a total of 686 CML patients with COVID-19. The vast majority of patients were in the chronic phase; seven patients were in the accelerated phase, and eight patients were in the blast phase. Disease severity was classified according to WHO criteria. Twenty-seven patients were managed at home, and 21 patients were in ICU (intensive care unit) during the hospital course. Twenty-six patients required oxygen therapy; among them, seven patients required intubation and mechanical ventilation, and six patients required non-invasive ventilation. Mortality was seen in 47 patients, and there were no reports of thrombotic events, but some patients developed AKI, autoimmune hemolytic anemia, rhabdomyolysis, and DKA during COVID-19. Limitations The major limitation is the lack of details about the use or hold of TKIs during SARS-CoV-2 infection in the majority of the reports. Also, the specific or predominant strain of SARS-CoV-2 was not mentioned. Few studies mentioned the variant of the virus, which make it difficult to compare the outcome of the different variant of the SARS-CoV-2 virus in patients with CML. Discussion/Conclusions Hematological cancers are associated with an increased risk of thrombosis. Thrombosis risk is expected to increase in patients with COVID-19; interestingly, patients with CML have not been reported to have a significant increase in the risk of thrombosis during COVID-19. The crucial point is, does TKI continuation during COVID-19 beneficial or harmful? Few patients continued TKIs during Covid-19 without serious adverse events. For patients who had the TKI continued, there were no mortality or serious adverse events. In vitro, TKIs were found to have a significant effect on inhibiting viral replication, which might be the reason behind the better outcome in CML patients infected with SARS-CoV-2 virus. On the other hand, there is a theoretical risk of increased severe infection in CML patients taking TKI due to targeted inhibition of kinases involved in immune cell function. This might result in suppressed cellular immune response that facilitates viral replication. Despite that, CML patients with COVID-19 have no significant increase in mortality or ICU admission compared to other hematological malignancies. in fact, our review showed that the mortality of CML patients with COVID-19 has significantly improved from 0.12% in the pre-vaccination period to 0.04% in the post-vaccination era. The available data indicates that, COVID-19's effect on patients with chronic myeloid leukemia (CML) still needs to be better understood due to the limited data.

Second-Generation Antipsychotics and VTE Risk

Introduction: It has been known for some time that antipsychotic medications are associated with an increased risk of venous thromboembolism (VTE) though mechanism of action has not yet been elucidated. However, it is not known if there are certain antipsychotics that are more associated with VTE than others, and with over 26 million prescriptions in 2020 of olanzapine, risperidone, aripiprazole and quetiapine combined the importance of identifying such an association, if it exists, is essential. To explore this a safety analysis was conducted of six second-generation antipsychotics using the FDA Adverse Event Reporting System (FAERS). Methods: The FAERS system was searched using the reaction terms ‘venous thrombosis’, 'deep vein thrombosis,' and 'pulmonary embolism.' Events were included if they occurred prior to 2023 and contained one of the aforementioned terms. Events could also include symptoms that could be reasonably associated with such a reaction - for example, hypoxia from pulmonary embolism (PE). Events were then narrowed further to include only those associated with a single second-generation antipsychotic - aripiprazole, clozapine, olanzapine, quetiapine, and ziprasidone. Data was then analyzed for demographic differences in weight and age of the patients using ANOVA, as well as frequency of VTE events using the proportional reporting ratio (PRR). Results: There were a total of 1155 VTE events amongst the six antipsychotics, out of 180824 total reported cases. Olanzapine (308) and quetiapine (273) had the most events overall as well as the most PEs (olanzapine 224, quetiapine 204), while risperidone had the most deep vein thromboses (DVT) (103). When analyzed using the PRR (for which ziprasidone was excluded due to low number of cases and events), olanzapine and quetiapine were disproportionally associated with an increased rate of VTE (2.57 and 2.22 respectively) and PE (2.71 and 2.42 respectively). Olanzapine and risperidone were associated with an increased rate of DVT (2.35 and 2.31 respectively). Though limited data was available on patient demographics, of that which was available (excluding ziprasidone), VTE patients on clozapine had significantly higher weights than those on quetiapine or olanzapine ( P = 0.01 and P = 0.004 respectively), while VTE patients on risperidone were significantly older than those taking aripiprazole or clozapine ( P = 0.003 and P = 0.03 respectively). There were otherwise no significant differences in age and weight among the different VTE antipsychotics groups. Discussion: This data suggests that the rate of VTE as reported to the FDA is unexpectedly high for those taking olanzapine and quetiapine as compared with other second-generation antipsychotics. Limitations of the study include reliance on accurate and complete reporting of events and potential for duplication of reports. Further investigation is needed into the differences amongst the antipsychotics in relation to VTE risk as well as further research into potential mechanism of action. Given how frequently these medications are prescribed, antipsychotics may represent an underrecognized significant contributor to rates of thrombosis.

Burden of Chemotherapy-Related Myelodysplastic Syndrome/Acute Myeloid Leukemia in the Chemotherapeutic Armamentarium

Introduction: Therapy related Myelodysplastic Syndrome and Acute Myeloid Leukemia (t-MDS/AML) is a well-established adverse event (AE) associated with conventional chemotherapy drugs and has historically carried a poorer prognosis when compared to de novo disease. Newer chemo medicines like PARP inhibitors have also been implicated in developing this complication. However, comprehensive real-world data is lacking pertaining to the AE burden relative to individual drug classes. Methods: We used the FDA Adverse Events Report System (FAERS) public dashboard to obtain the data. Data was available for the years 1970 - 2023. We retrieved the number of events that were reported as “Myelodysplastic Syndrome” or “Acute Myeloid Leukemia” for individual chemotherapy classes that have historically been known to cause t-MDS/AML. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with its 95% confidence interval (CI). Results: The drug class with the highest ROR of MDS/AML was the topoisomerase inhibitors - ROR 2.38 (95% CI 2.27-2.49). Intercalating agents like anthracyclines and mitoxantrone had the next highest ROR of 2.12 (95% CI 2.04 - 2.21). The novel drug class PARP inhibitors had the third most burden of t-MDS/AML with an ROR of 1.57 (95% CI 1.46 - 1.69). Table 1. depicts the individual drug classes and their ROR for associated MDS/AML. Table 1 depicts the individual drug classes and their ROR for associated MDS/AML. Conclusions: From this retrospective analysis, we identified that among all the chemotherapy drug classes, the topoisomerase II inhibitors were associated with the highest burden of t-MDS/AML, followed by intercalating agents and PARP inhibitors. Further data is essential to identify the patient characteristics associated with higher risk of developing this dreaded complication. This could improve patient-counseling prior to treatment initiation, assist with alternate drug choices when applicable, and perhaps also aid in developing strategies for closer monitoring in high-risk patients.